Oral Compositions

ABSTRACT

Oral compositions useful for controlling dental plaque and gingivitis and for preventing caries are produced comprising a cationic antimicrobial agent and a combination of anti-stain agents which reduce the staining effect of the cationic antimicrobial.

This is a division of Ser. No. 889,205 filed Mar. 23, 1978.

The present invention is concerned with oral compositions useful forcontrolling dental plaque and gingivitis and for preventing caries. Theactive agent is a cationic antimicrobial agent, such as bisbiguanides orquaternary ammonium compounds, which agents are known in the art to beuseful for such purposes. It is also known in the art that cationicantimicrobial agents such as bisbiguanides and quaternary ammoniumcompounds have the disadvantage of staining teeth. The present inventionprovides an oral composition utilizing bisbiguanides or quaternaryammonium compounds together with a combination of anti-stain agentswhich exert an additive effect on stain reduction thus providing greaterstain reduction than is provided by the individual anti-stain agentsalone.

It is known in the art that bisbiguanides inhibit the formation ofplaque and caries and that anti-calculus agents may be combinedtherewith to inhibit the tendency of the bisbiguanides to stain the oralsurfaces. (See U.S. Pat. No. No. 3,934,002.) Among the anti-calculusagents disclosed in said patent are quaternary ammonium compounds, zincphenolsulphate, hydroxyquinoline, citric acid, lactic acid andpharmaceutically acceptable salts thereof.

The present invention is based on the surprising discovery thatcombining a nonionic surfactant, which exhibits some anti-stain actionitself, with an amino acid, a di- and/or tri-carboxylic acid or afuranolactone substantially reduces the staining on oral surfaces of thebisbiguanide or quaternary ammonium active agents of the instantcompositions.

More particularly, the present invention comprises an oral compositionuseful for controlling dental plaque and gingivitis and for preventingcaries which comprises an effective amount of a bisbiguanide orquaternary ammonium compound which is capable of controlling dentalplaque and gingivitis and preventing caries and an anti-staincomposition which comprises a nonionic surfactant capable of reducingthe staining tendency of said bisbiguanide or quaternary ammoniumcompound and a member selected from the group consisting of an aminoacid, a dicarboxylic acid, a tri-carboxylic acid or a mixture of di- andtri-carboxylic acids and a furanolactone, each of which individuallyinhibits the tendency of bisbiguanides and quaternary compounds to stainoral surfaces.

According to one embodiment of the present invention the antimicrobialagent is a bisbiguanide. More particularly, the1,1'-bridged-bis[5-higher-alkylbiguanides] and 1,1'-bridged-bia[3-higheralkylguanidines] represented in the free base form by the followingstructural formula and described in detail in U.S. Pat. No. 3,468,898have been found to be particularly useful according to the presentinvention: ##STR1## wherein the bivalent bridge A is a member of thegroup consisting of: (a) alkylene of from 2 to 12 carbon atoms havingthe valence bonds attached to different carbon atoms,

(b) --(CH₂)_(m) --Y--(CH₂)_(n) --wherein m and n each represent aninteger from 2 to 6 and Y is a member of the group consisting of O andS, ##STR2## wherein Z and Z' are each alkylene of from 1 to 3 carbonatoms, ##STR3## wherein Q is a member of the group consisting of --O--,--S--, --SO-- and --SO₂ --, and ##STR4## R is a member of the groupconsisting of (a) alkyl of from 6 to 16 carbon atoms, and

(b) alkyl-Y-alkylene, wherein Y is a member of the group consisting of Oand S;

R' is a member of the group consisting of H and lower alkyl; and

x is an integer from 1 to 2.

According to another embodiment of the present invention theantimicrobial agent is a quaternary ammonium compound.

According to another embodiment of the present invention the amount ofantimicrobial agent is from 0.01% to about 1.0% w/w based on the totalweight of ingredients or w/v when in liquid form.

According to another embodiment of the present invention the amount ofanti-stain composition is from 0.1% to 3.0% w/w or w/v.

According to another embodiment of the present invention the pH of thecomposition is from about 4.8 to about 8.0.

According to another embodiment of the present invention thebisbiguanide is 1,6-bis (2-ethylhexyldiguanido hexane) dihydrochloride[alexidine dihydrochloride]; 1,6-bis (2-ethylhexyl diguanido hexane)dihydrofluoride; 1,6-bis (2-ethylhexyl diguanido octane)dihydrochloride; 1,6-bis (2-ethylhexyl diguanido nonane)dihydrochloride; 1,6-bis (2-ethylhexyl diguanido dodecane)dihydrochloride; or 1,6-di (4-chlorophenyl diguanido hexane)dihydrochloride or the diacetate or digluconate salt thereof. Alexidinedihydrochloride is especially preferred.

According to another embodiment of the present invention the quaternaryammonium compound is dodecyl dimethyl-(2-phenoxyethyl)-ammonium;benzyldimethyl (2-)2-(p-1,3,3-tetramethyl butyl phenoxy)ethoxyl)ethyl)ammonium; p-bromobenzyl-dimethyl-γ-(2'-isopropyl, 4'-chloro,5'-methylphenoxy)-propyl ammonium; 1-hexadecyl-pyridinium salt;acylcholaminoformylmethyl pyridinium chloride-iodide complex;1-alkyl-4-aminoquinaldinium salt; decamethylene bis(4-aminoquinaldinumchloride) or hexadecamethylene bis (isoquinolinium chloride).

According to another embodiment of the present invention the nonionicsurfactant is a mono- or di-glyceride; a sorbitan fatty acid ester; apolyoxyethylene sorbitan fatty acid ester; a polyoxyethylene sorbitolester; a polyoxyethylene acid; a polyoxyethylene alcohol; a poly(oxyethylene)-poly (oxypropylene)poly (oxyethylene) polymer; apolyoxyethylene N-substituted fatty acid amide; a poly-(ethylene glycol)p-nonyl phenyl ether; an octyl phenoxy poly ethoxy-ethanol; or a polysiloxane.

According to another embodiment of the present invention the amino acid,which should be compatible with the antimicrobial agent and the nonionicsurfactant, is aspartic acid, cysteine, glutamic acid, para-aminobenzoic acid, p-hydroxy benzoic acid, α-aminoadipic acid, N-(p-aminobenzoyl) glutamic acid, p-amino hippuric acid or p-amino phenylaceticacid.

According to another embodiment of the present invention the carboxylicacid, which should be compatible with the antimicrobial agent and thenonionic surfactant, is citric acid, α-ketoglutaric acid, malic acid,succinic acid, oxalic acid, adipic acid, fumaric acid, glutaric acid,maleic acid, tartaric acid or malonic acid. Citric acid is preferred.

According to another embodiment of the present invention thefuranolactone, which should be compatible with the antimicrobial agentand the nonionic surfactant, is ascorbic acid.

According to another embodiment of the present invention, the aminoacid, the carboxylic acid and the furanolactone are present in a molarexcess of about 10:1 to about 25:1 over the cationic antimicrobialagent.

The usual flavoring agents, binders, sudsing agents, humectants,alcohols, fragrances, abrasives and excipients known in the art can beadded to the compositions of the present invention.

When the oral composition of the present invention is in the form of amouthwash, oral rinse or gargle, the composition is brought into contactwith the oral cavity and then is expectorated. A dose of 15 to 20 ml.for adults and about 10 ml. for children is generally sufficient whenused on a daily basis.

When the instant composition is in the form of a dentifrice, such as apaste, powder, concentrate, solution or gel for direct application tothe teeth, it can be used in the normal manner in which a toothpaste isused. When the oral composition of the present invention is in aconcentrate for use with mechanical irrigation devices such as a waterjet or "water pik" type device, approximately 10 to 15 ml should besprayed into the mouth and circulated in the oral cavity and then beexpectorated. When the present composition is in the form of a breathfreshener, either pump spray or aerosol type, approximately 10 to 15 ml.should be sprayed into the mouth, circulated therethrough and beexpectorated. When the composition of the present invention is in theform of a troche or a lozenge, it should be allowed to dissolve in themouth and then be expectorated.

The following nonlimitative examples more particularly illustrate thepresent invention.

Oral compositions in solution form were produced as follows:

    __________________________________________________________________________    Ingredients    % w/v % w/v % w/v % w/v                                        __________________________________________________________________________                   Examples                                                                      1     2     3     4                                            Alexidine . 2HCl                                                                             0.01-0.2                                                                            0.01-0.2                                                                            0.01-0.2                                                                            0.01-0.2                                     Alcohol USP    15.0-20.0                                                                           15.0-20.0                                                                           15.0-20.0                                                                           15.0-20.0                                    Glycerin       10.0  10.0  10.0  10.0                                         Sodium Saccharin                                                                             0.002-0.04                                                                          0.002-0.04                                                                          0.002-0.04                                                                          0.002-0.04                                   Brij-35 S.P. (1)                                                                             0.1-1.5                                                                             --    --    --                                           Tween-80 (2)   --    0.05-1.0                                                                            --    --                                           Emsorb 6912 (3)                                                                              --    --    0.1-1.5                                                                             --                                           Pluronic F-108 (4)                                                                           --    --    --    0.1-1.5                                      P-Aminobenzoic Acid                                                                          0.05-1.0                                                                            0.05-1.0                                                                            0.05-1.0                                                                            0.05-1.0                                     Water to       100 ml                                                                              100 ml                                                                              100 ml                                                                              100 ml                                       NaOH to adjust pH                                                                            4.8-5.1                                                                             4.8-5.1                                                                             4.8-5.1                                                                             4.8-5.1                                      Flavor                                                                                       As desired                                                     Color                                                                         __________________________________________________________________________                   Examples                                                                      5     6     7     8                                            Alexidine . 2HCl                                                                             0.01-0.2                                                                            0.01-0.2                                                                            0.01-0.2                                                                            0.01-0.2                                     Alcohol USP    15.0-20.0                                                                           15.0-20.0                                                                           15.0-20.0                                                                           15.0-20.0                                    Glycerin       10.0  10.0  10.0  10.0                                         Sodium Saccharin                                                                             0.002-0.04                                                                          0.002-0.04                                                                          0.002-0.04                                                                          0.002-0.04                                   Brij-35 S.P. (1)                                                                             0.1-1.5                                                                             --    --    --                                           Tween-80 (2)   --    0.05-1.0                                                                            --    --                                           Emsorb 6912 (3)                                                                              --    --    0.1-1.5                                                                             --                                           Pluronic F-108 (4)                                                                           --    --    --    0.1-1.5                                      Aspartic Acid  0.05-1.5                                                                            0.05-1.5                                                                            0.05-1.5                                                                            0.05-1.5                                     Water to       100 ml                                                                              100 ml                                                                              100 ml                                                                              100 ml                                       NaOH to adjust pH                                                                            4.8-5.1                                                                             4.8-5.1                                                                             4.8-5.1                                                                             4.8-5.1                                      Flavor                                                                                       As desired                                                     Color                                                                         __________________________________________________________________________                   Examples                                                                      9     10    11    12                                           Alexidine . 2HCl                                                                             0.01-0.2                                                                            0.01-0.2                                                                            0.01-0.2                                                                            0.01-0.2                                     Alcohol USP    15.0-20.0                                                                           15.0-20.0                                                                           15.0-20.0                                                                           15.0-20.0                                    Glycerin       10.0  10.0  10.0  10.0                                         Sodium Saccharin                                                                             0.002-0.04                                                                          0.002-0.04                                                                          0.002-0.04                                                                          0.002-0.04                                   Brij-35 S.P. (1)                                                                             0.1-1.5                                                                             --    --    --                                           Tween-80 (2)   --    0.05-1.0                                                                            --    --                                           Emsorb 6912 (3)                                                                              --    --    0.1-1.5                                                                             --                                           Pluronic F-108 (4)                                                                           --    --    --    0.1-1.5                                      Citric Acid    0.05-2.0                                                                            0.05-2.0                                                                            0.05-2.0                                                                            0.05-2.0                                     Water to       100 ml                                                                              100 ml                                                                              100 ml                                                                              100 ml                                       NaOH to adjust pH                                                                            4.8-5.1                                                                             4.8-5.1                                                                             4.8-5.1                                                                             4.8-5.1                                      Flavor                                                                                       As desired                                                     Color                                                                         __________________________________________________________________________                   Examples                                                                      13    14    15    16                                           Alexidine . 2HCl                                                                             0.01-0.2                                                                            0.01-0.2                                                                            0.01-0.2                                                                            0.01-0.2                                     Alcohol USP    15.0-20.0                                                                           15.0-20.0                                                                           15.0-20.0                                                                           15.0-20.0                                    Glycerin       10.0  10.0  10.0  10.0                                         Sodium Saccharin                                                                             0.002-0.04                                                                          0.002-0.04                                                                          0.002-0.04                                                                          0.002-0.04                                   Brij-35 S.P. (1)                                                                             0.1-1.5                                                                             --    --    --                                           Tween-80 (2)   --    0.05-1.0                                                                            --    --                                           Emsorb 6912 (3)                                                                              --    --    0.1-1.5                                                                             --                                           Pluronic F-108 (4)                                                                           --    --    --    0.1-1.5                                      Fumaric Acid   0.05-1.0                                                                            0.05-1.0                                                                            0.05-1.0                                                                            0.05-1.0                                     Water to       100 ml                                                                              100 ml                                                                              100 ml                                                                              100 ml                                       NaOH to adjust pH                                                                            4.8-5.1                                                                             4.8-5.1                                                                             4.8-5.1                                                                             4.8-5.1                                      Flavor                                                                                       As desired                                                     Color                                                                         __________________________________________________________________________                   Examples                                                                      17    18    19    20                                           Alexidine . 2HCl                                                                             0.01-0.2                                                                            0.01-0.2                                                                            0.01-0.2                                                                            0.01-0.2                                     Alcohol USP    15.0-20.0                                                                           15.0-20.0                                                                           15.0-20.0                                                                           15.0-20.0                                    Glycerin       10.0  10.0  10.0  10.0                                         Sodium Saccharin                                                                             0.002-0.04                                                                          0.002-0.04                                                                          0.002-0.04                                                                          0.002-0.04                                   Brij-35 S.P. (1)                                                                             0.1-1.5                                                                             --    --    --                                           Tween-80 (2)   --    0.05-1.0                                                                            --    --                                           Emsorb 6912 (3)                                                                              --    --    0.1-1.5                                                                             --                                           Pluronic F-108 (4)                                                                           --    --    --    0.1-1.5                                      Gantrez AN-119 (5)                                                                           0.05-0.5                                                                            0.05-0.5                                                                            0.05-0.5                                                                            0.05-0.5                                     Water to       100 ml                                                                              100 ml                                                                              100 ml                                                                              100 ml                                       NaOH to adjust pH                                                                            4.8-5.1                                                                             4.8-5.1                                                                             4.8-5.1                                                                             4.8-5.1                                      Flavor                                                                                       As desired                                                     Color                                                                         __________________________________________________________________________                   Examples                                                                      21    22    23    24                                           Alexidine . 2HCl                                                                             0.01-0.2                                                                            0.01-0.2                                                                            0.01-0.2                                                                            0.01-0.2                                     Alcohol USP    15.0-20.0                                                                           15.0-20.0                                                                           15.0-20.0                                                                           15.0-20.0                                    Glycerin       10.0  10.0  10.0  10.0                                         Sodium Saccharin                                                                             0.002-0.04                                                                          0.002-0.04                                                                          0.002-0.04                                                                          0.002-0.04                                   Brij-35 S.P. (1)                                                                             0.1-1.5                                                                             --    --    --                                           Tween-80 (2)   --    0.05-1.0                                                                            --    --                                           Emsorb 6912 (3)                                                                              --    --    0.1-1.5                                                                             --                                           Pluronic F-108 (5)                                                                           --    --    --    0.1-1.5                                      Glutamic Acid  0.05-1.0                                                                            0.05-1.0                                                                            0.05-1.0                                                                            0.05-1.0                                     Water to       100 ml                                                                              100 ml                                                                              100 ml                                                                              100 ml                                       NaOH to adjust pH                                                                            4.8-5.1                                                                             4.8-5.1                                                                             4.8-5.1                                                                             4.8-5.1                                      Flavor                                                                                       As desired                                                     Color                                                                         __________________________________________________________________________                   Examples                                                                      25    26    27    28                                           Alexidine . 2HCl                                                                             0.01-0.2                                                                            0.01-0.2                                                                            0.01-0.2                                                                            0.01-0.2                                     Alcohol USP    15.0-20.0                                                                           15.0-20.0                                                                           15.0-20.0                                                                           15.0-20.0                                    Glycerin       10.0  10.0  10.0  10.0                                         Sodium Saccharin                                                                             0.002-0.04                                                                          0.002-0.04                                                                          0.002-0.04                                                                          0.002-0.04                                   Brij-35 S.P. (1)                                                                             0.1-1.5                                                                             --    --    --                                           Tween-80 (2)   --    0.05-1.0                                                                            --    --                                           Emsorb 6912 (3)                                                                              --    --    0.1-1.5                                                                             --                                           Pluronic F-108 (4)                                                                           --    --    --    0.1-1.5                                      p-hydroxy benzoic                                                                            0.05-0.5                                                                            0.05-0.5                                                                            0.05-0.5                                                                            0.05-0.5                                     acid                                                                          Water to       100 ml                                                                              100 ml                                                                              100 ml                                                                              100 ml                                       NaOH to adjust pH                                                                            4.8-5.1                                                                             4.8-5.1                                                                             4.8-5.1                                                                             4.8-5.1                                      Flavor                                                                                       As desired                                                     Color                                                                         __________________________________________________________________________                   Examples                                                                      29    30    31    32                                           Alexidine . 2HCl                                                                             0.01-0.2                                                                            0.01-0.2                                                                            0.01-0.2                                                                            0.01-0.2                                     Alcohol USP    15.0-20.0                                                                           15.0-20.0                                                                           15.0-20.0                                                                           15.0-20.0                                    Glycerin       10.0  10.0  10.0  10.0                                         Sodium Saccharin                                                                             0.002-0.04                                                                          0.002-0.04                                                                          0.002-0.04                                                                          0.002-0.04                                   Brij-35 S.P. (1)                                                                             0.1-1.5                                                                             --    --    --                                           Tween-80 (2)   --    0.05-1.0                                                                            --    --                                           Emsorb 6912 (3)                                                                              --    --    0.1-1.5                                                                             --                                           Pluronic F-108 (4)                                                                           --    --    --    0.1-1.5                                      Iminodiacetic Acid                                                                           0.05-0.5                                                                            0.05-0.5                                                                            0.05-0.5                                                                            0.05-0.5                                     Water to       100 ml                                                                              100 ml                                                                              100 ml                                                                              100 ml                                       NaOH to adjust pH                                                                            4.8-5.1                                                                             4.8-5.1                                                                             4.8-5.1                                                                             4.8-5.1                                      Flavor                                                                                       As desired                                                     Color                                                                         __________________________________________________________________________                   Examples                                                                      33    34    35    36                                           Alexidine . 2HCl                                                                             0.01-0.2                                                                            0.01-0.2                                                                            0.01-0.2                                                                            0.01-0.2                                     Alcohol USP    15.0-20.0                                                                           15.0-20.0                                                                           15.0-20.0                                                                           15.0-20.0                                    Glycerin       10.0  10.0  10.0  10.0                                         Sodium Saccharin                                                                             0.002-0.04                                                                          0.002-0.04                                                                          0.002-0.04                                                                          0.002-0.04                                   Brij-35 S.P. (1)                                                                             0.1-1.5                                                                             --    --    --                                           Tween-80 (2)   --    0.05-1.0                                                                            --    --                                           Emsorb 6912 (3)                                                                              --    --    0.1-1.5                                                                             --                                           Pluronic F-108 (4)                                                                           --    --    --    0.1-1.5                                      Malonic Acid   0.05-1.0                                                                            0.05-1.0                                                                            0.05-1.0                                                                            0.05-1.0                                     Water to       100 ml                                                                              100 ml                                                                              100 ml                                                                              100 ml                                       NaOH to adjust pH                                                                            4.8-5.1                                                                             4.8-5.1                                                                             4.8-5.1                                                                             4.8-5.1                                      Flavor                                                                                       As desired                                                     Color                                                                         __________________________________________________________________________                   Examples                                                                      37    38    39    40                                           Alexidine . 2HCl                                                                             0.01-0.2                                                                            0.01-0.2                                                                            0.01-0.2                                                                            0.01-0.s                                     Alcohol USP    15.0-20.0                                                                           15.0-20.0                                                                           15.0-20.0                                                                           15.0-20.0                                    Glycerin       10.0  10.0  10.0  10.0                                         Sodium Saccharin                                                                             0.002-0.04                                                                          0.002-0.04                                                                          0.002-0.04                                                                          0.002-0.04                                   Brij-35 S.P. (1)                                                                             0.1- 1.5                                                                            --    --    --                                           Tween-80 (2)   --    0.05-1.0                                                                            --    --                                           Emsorb 6912 (3)                                                                              --    --    0.1-1.5                                                                             --                                           Pluronic F-108 (4)                                                                           --    --    --    0.1-1.5                                      Mono-tris(hydroxy                                                                            0.05-1.0                                                                            0.05-1.0                                                                            0.05-1.0                                                                            0.05-1.0                                     methyl)amino methane                                                          Water to       100 ml                                                                              100 ml                                                                              100 ml                                                                              100 ml                                       NaOH to adjust pH                                                                            4.8-5.1                                                                             4.8-5.1                                                                             4.8-5.1                                                                             4.8-5.1                                      Flavor                                                                                       As desired                                                     Color                                                                         __________________________________________________________________________                   Examples                                                                      41    42    43    44                                           Alexidine . 2HCl                                                                             0.01-0.2                                                                            0.01-0.2                                                                            0.01-0.2                                                                            0.01-0.2                                     Alcohol USP    15.0-20.0                                                                           15.0-20.0                                                                           15.0-20.0                                                                           15.0-20.0                                    Glycerin       10.0  10.0  10.0  10.0                                         Sodium Saccharin                                                                             0.002-0.04                                                                          0.002-0.04                                                                          0.002-0.04                                                                          0.002-0.04                                   Brij-35 S.P. (1)                                                                             0.1-1.5                                                                             --    --    --                                           Tween-80 (2)   --    0.05-1.0                                                                            --    --                                           Emsorb 6912 (3)                                                                              --    --    0.1-1.5                                                                             --                                           Pluronic F-108 (4)                                                                           --    --    --    0.1-1.5                                      Pimelic Acid   0.05-0.5                                                                            0.05-0.5                                                                            0.05-0.5                                                                            0.05-0.5                                     Water to       100 ml                                                                              100 ml                                                                              100 ml                                                                              100 ml                                       NaOH to adjust pH                                                                            4.8-5.1                                                                             4.8-5.1                                                                             4.8-5.1                                                                             4.8-5.1                                      Flavor                                                                                       As desired                                                     Color                                                                         __________________________________________________________________________                   Examples                                                                      45    46    47    48                                           Alexidine . 2HCl                                                                             0.01-0.2                                                                            0.01-0.2                                                                            0.01-0.2                                                                            0.01-0.2                                     Alcohol USP    15.0-20.0                                                                           15.0-20.0                                                                           15.0-20.0                                                                           15.0.20.0                                    Glycerin       10.0  10.0  10.0  10.0                                         Sodium Saccharin                                                                             0.002-0.04                                                                          0.002-0.04                                                                          0.002-0.04                                                                          0.002-0.04                                   Brij-35 S.P. (1)                                                                             0.1-1.5                                                                             --    --    --                                           Tween-80 (2)   --    0.05-1.0                                                                            --    --                                           Emsorb 6912 (3)                                                                              --    --    0.1-1.5                                                                             --                                           Pluronic F-108 (4)                                                                           --    --    --    0.1-1.5                                      2,3-Pyrazinedicarb-                                                                          0.05-0.5                                                                            0.05-0.5                                                                            0.05-0.5                                                                            0.05-0.5                                     oxylic acid                                                                   Water to       100 ml                                                                              100 ml                                                                              100 ml                                                                              100 ml                                       NaOH to adjust pH                                                                            4.8-5.1                                                                             4.8-5.1                                                                             4.8-5.1                                                                             4.8-5.1                                      Flavor                                                                                       As desired                                                     Color                                                                         __________________________________________________________________________     (1) Polyoxyethylene (23) laurylether                                          (2) Polysorbate80 USP                                                         (3) Polyoxyethylene (20) Sorbitan Monoisostearate                             (4) Poly (oxyethylene) poly (oxypropylene) block copolymer                    (5) Copolymer of methyl vinyl ether and maleic anhydride                 

The following in vitro experiments demonstrate the anti-stain effect ofthe combination of anti-stain agents according to the present invention.

Combinations of Brij 35 S.P. and amino or carboxylic acids demonstratedreduction in staining resulting from alexidine dihydrochloride of from41% to 69%.

Methods: The substrate for the in vitro stain assay was a saliva-coatedhydroxylapatite and the staining agent was 5% tannic acid. Eachformulation was tested in triplicate. The table set forth below showsthe formulation tested and the percent of inhibition of alexidinedihydrochloride mediated stain.

    ______________________________________                                                                       % Inhibition                                                         Mole     of Alexidine . 2HCl                            Formulation   pH      Ratio.sup.a                                                                            Mediated Stain                                 ______________________________________                                        Brij 35 S.P.  4.8     --       30%                                            Citric Acid   2.4              32%                                                                  13.8                                                    Brij 35 S.P. +                                                                Citric Acid   5.1              69%                                            Glutamic Acid 3.1              40%                                                                  19.8                                                    Brij 35 S.P. +                                                                Glutamic Acid 5.1              55%                                            p-Aminobenzoic Acid                                                                         3.5              22%                                                                  21.2                                                    Brij 35 S.P. + p-Amino-                                                       benzoic acid  5.1              65%                                            Fumaric Acid  2.2              44%                                                                  25.0                                                    Brij 35 S.P. +                                                                Fumaric Acid  5.0              65%                                            Aspartic Acid 2.8              34%                                                                  21.8                                                    Brij 35 S.P. +                                                                Aspartic Acid 5.1              41%                                            ______________________________________                                         .sup.a Ratio of amino or carboxylic acid to alexidine . 2HCl.            

What is claimed is:
 1. In an oral composition for controlling dentalplaque and gingivitis and for preventing caries which comprises from0.01% to about 1.0% w/v of a cationic antimicrobial agent useful forcontrolling dental plaque and gingivitis and for preventing cariesselected from the group having a tendency to stain teeth consisting of abisbiguanide and a quaternary ammonium compound, the improvement whichcomprises from 0.1% to 3.5% of a composition which comprises aneffective amount of a nonionic surfactant exhibiting anti-staincharacteristics and an effective amount of a member selected from thegroup consisting of an amino acid exhibiting anti-stain characteristics,a dicarboxylic aci and a tricarboxylic acid or a mixture thereof whichexhibits anti-stain characteristics said member being present in a molarexcess of about 10:1 to about 20:1 over the cationic anti-microbialagent.
 2. A composition according to claim 1 wherein the antimicrobialagent is a bisbiguanide.
 3. A composition according to claim 1 whereinthe antimicrobial agent is a quaternary ammonium compound.
 4. Acomposition according to claim 1 wherein the amount of antimicrobialagent is from 0.01% to about 1.0% w/w or w/v.
 5. A composition accordingto claim 1 wherein the amount of anti-stain composition is from 0.1% to1.0% w/w or w/v.
 6. A composition according to claim 1 wherein the pH ofthe composition is from about 5.0 to about 8.0.
 7. A compositionaccording to claim 1 wherein the agent is a bisbiguanide which is1,6-bis (2-ethylhexyl diguanido hexane) dihydrochloride; 1,6-bis(2-ethylhexyl diguanido hexane) dihydrofluoride; 1,6-bis (2-ethylhexyldiguanido octane) dihydrochloride; 1,6-bis (2-ethylhexyl diguanidononane) dihydrochloride; 1,6-bis (2-ethylhexyl diguanido dodecane)dihydrochloride; or 1,6-di (4-chlorophenyl diguanido hexane)dihydrochloride or the diacetate or digluconate salt thereof.
 8. Acomposition according to claim 3 wherein the agent is a quaternaryammonium compound which is dodcecyl dimethyl-(2-phenoxyethyl)-ammonium;benzyldimethyl (2-)2-(p-1,3,3-tetramethyl butyl phenoxy)ethoxyl)ethyl)ammonium; p-bromobenzyl-dimethyl-γ-(2'-isopropyl, 4'-chloro, 5'-methylphenoxy)propyl ammonium; 1-hexadecyl-pyridinium salt;acylcholaminoformyl-methyl pyridinium chloride-iodide complex;1-alkyl-4-aminoquinaldinium salt; decamethylene bis(4-aminoquinaldinumchloride) or hexadecamethylene bis (isoquinolinium chloride).
 9. Acomposition according to claim 1 wherein the nonionic surfactant is amono- or di-glyceride; a sorbitan fatty acid ester; a polyoxyethylenesorbitan fatty acid ester; a polyoxyethylene sorbitol ester; apolyoxyethylene acid; a polyoxyethylene alcohol; a poly(oxyethylene)-poly(oxypropylene)-poly (oxyethylene) polymer; apolyoxyethylene N-substituted fatty acid amide; a poly(ethylene glycol)p-nonyl phenyl ether; an octyl phenoxy poly ethoxy-ethanol; or a polysiloxane.
 10. A composition according to claim 1 wherein the amino acidis aspartic acid, cysteine, glutamic acid, paraamino benzoic acid,α-aminoadipic acid, N-(p-amino benzoyl) glutamic acid, p-amino hippuricacid or p-amino phenylacetic acid.
 11. A composition according to claim1 wherein the carboxylic acid is citric acid, α-ketoglutaric acid, malicacid, succinic acid, oxalic acid, adipic acid, fumaric acid, glutaricacid, maleic acid, tartaric acid or malonic acid.
 12. A compositionaccording to claim 1 wherein the amino acid, the carboxylic acid or thefuranolactone is present in a molar excess of about 10:1 to about 25:1over the cationic antimicrobial agent.
 13. A composition according toclaim 1 in mouthwash form.
 14. A composition according to claim 1 inoral rinse form.
 15. A composition according to claim 1 in dentifriceform.
 16. A composition according to claim 1 in tooth powder form.
 17. Acomposition according to claim 1 in oral solution form.
 18. Acomposition according to claim 1 in gel form.
 19. A compositionaccording to claim 1 in a form suitable for dispensing through a waterjet.
 20. A composition according to claim 1 in a breath freshener form.21. A composition according to claim 1 in an aerosol form.
 22. Acomposition according to claim 1 in a gargle form.
 23. A compositionaccording to claim 1 in the form of a troche.
 24. A compositionaccording to claim 1 in lozenge form.